NeuroX, a fast and efficient genotyping platform for investigation of neurodegenerative diseases
NeuroX, a fast and efficient genotyping platform for investigation of neurodegenerative diseases
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DOI：
10.1016/j.neurobiolaging.2014.07.028
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发表时间：
2015-03-01
影响因子：
4.2
通讯作者：
Singleton, Andrew B.
中科院分区：
文献类型：
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作者：
Nalls, Mike A.;Bras, Jose;Singleton, Andrew B.
我们的目标是设计一个基因分型平台，允许在与常见神经退行性疾病相关的基因突变和风险因素的背景下对样本进行快速遗传表征。该平台需要相对负担得起，部署迅速，并使用通用和可访问的技术。作为这个项目的核心，我们想让平台的内容不受限制地向任何调查人员开放。在设计这个阵列时，我们优先考虑了许多类型的遗传变异性，例如已知的风险等位基因，致病突变，推定的风险等位基因和其他功能重要的变异。该阵列的主要目的是允许快速筛查致病突变的样本和风险因素的大规模人群研究。值得注意的是，一个明确的目标是广泛提供这一阵列，以促进疾病之间和疾病内部的数据共享。由此产生的阵列NeuroX是高质量基因分型的显着成本和时间效益的解决方案。NeuroX包含约240，000个变体的标准Illumina外显子组内容的主干，以及超过24，000个专注于神经系统疾病的自定义内容变体。使用12个样本格式的芯片和常规的Infinium基础设施，每个样本产生的数据约为50 - 60美元;因此，基因分型是快速的，许多研究人员都可以使用。在这里，我们描述了NeuroX的设计，讨论了NeuroX在分析罕见和常见风险变体中的实用性，并介绍了质量控制指标和用于分析NeuroX衍生数据的简短入门。爱思唯尔公司出版
Our objective was to design a genotyping platform that would allow rapid genetic characterization of samples in the context of genetic mutations and risk factors associated with common neurodegenerative diseases. The platform needed to be relatively affordable, rapid to deploy, and use a common and accessible technology. Central to this project, we wanted to make the content of the platform open to any investigator without restriction. In designing this array we prioritized a number of types of genetic variability for inclusion, such as known risk alleles, disease-causing mutations, putative risk alleles, and other functionally important variants. The array was primarily designed to allow rapid screening of samples for disease-causing mutations and large population studies of risk factors. Notably, an explicit aim was to make this array widely available to facilitate data sharing across and within diseases. The resulting array, NeuroX, is a remarkably cost and time effective solution for high-quality genotyping. NeuroX comprises a backbone of standard Illumina exome content of approximately 240,000 variants, and over 24,000 custom content variants focusing on neurologic diseases. Data are generated at approximately $50-$60 per sample using a 12-sample format chip and regular Infinium infrastructure; thus, genotyping is rapid and accessible to many investigators. Here, we describe the design of NeuroX, discuss the utility of NeuroX in the analyses of rare and common risk variants, and present quality control metrics and a brief primer for the analysis of NeuroX derived data. Published by Elsevier Inc.